Adolescent stress-induced epigenetic control of dopaminergic neurons via glucocorticoids

Academic Article

Abstract

  • Environmental stressors during childhood and adolescence influence postnatal brain maturation and human behavioral patterns in adulthood. Accordingly, excess stressors result in adult-onset neuropsychiatric disorders. We describe an underlying mechanism in which glucocorticoids link adolescent stressors to epigenetic controls in neurons. In a mouse model of this phenomenon, a mild isolation stress affects the mesocortical projection of dopaminergic neurons in which DNA hypermethylation of the tyrosine hydroxylase gene is elicited, but only when combined with a relevant genetic risk for neuropsychiatric disorders. These molecular changes are associated with several neurochemical and behavioral deficits that occur in this mouse model, all of which are blocked by a glucocorticoid receptor antagonist. The biology and phenotypes of the mouse models resemble those of psychotic depression, a common and debilitating psychiatric disease.
  • Published In

  • Science  Journal
  • Digital Object Identifier (doi)

    Author List

  • Niwa M; Jaaro-Peled H; Tankou S; Seshadri S; Hikida T; Matsumoto Y; Cascella NG; Kano SI; Ozaki N; Nabeshima T
  • Start Page

  • 335
  • End Page

  • 339
  • Volume

  • 339
  • Issue

  • 6117